Anti-heat shock protein 60 autoantibodies induce atherosclerosis in apolipoprotein E-deficient mice via endothelial damage.

نویسندگان

  • Georgios Foteinos
  • Ali R Afzal
  • Kaushik Mandal
  • Marjan Jahangiri
  • Qingbo Xu
چکیده

BACKGROUND Accumulating evidence established a positive association of anti-heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis in humans. However, whether these autoantibodies play a causal role in the development of atherosclerosis is unknown. METHODS AND RESULTS In the present study, anti-HSP60 autoantibodies from blood of patients with coronary heart disease were isolated by affinity chromatography and injected into the tail vein of apolipoprotein E-deficient mice. Atherosclerotic lesions in aortas were significantly increased 8 weeks after injection. Furthermore, administration of a specific mouse monoclonal antibody (II-13) recognizing amino acid residues 288 to 366 of HSP60 effectively induced atherosclerotic lesions in apolipoprotein E-deficient mice. II-13 injection resulted in endothelial cell damage, followed by increased leukocyte attachment and accumulation of macrophages and smooth muscle cells in lesions. Interestingly, II-13-induced atherosclerosis was blocked by pretreatment of animals with F(ab)2 segments derived from the antibody, but not mouse IgG F(ab)2. CONCLUSIONS Autoantibodies recognizing amino acid residues 288 to 366 of HSP60 induce atherosclerosis via the mechanisms of autoimmune reactions to HSP60 expressed on arterial endothelial cells, which can be prevented by F(ab)2 segments derived from these antibodies.

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عنوان ژورنال:
  • Circulation

دوره 112 8  شماره 

صفحات  -

تاریخ انتشار 2005